Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner

Haissam Abou-Saleh, Ahmed Hachem, Daniel Yacoub, Marc Antoine Gillis, Yahye Merhi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The role of endothelial progenitor cells (EPCs) in vascular repair is related to their recruitment at the sites of injury and their interaction with different components of the circulatory system. We have previously shown that EPCs bind and inhibit platelet function and impair thrombus formation via prostacyclin secretion, but the role of EPC binding to platelet P-selectin in this process has not been fully characterized. In the present study, we assessed the impact of EPCs on thrombus formation and we addressed the implication of P-selectin in this process. Methods: EPCs were generated from human peripheral blood mononuclear cells cultured on fibronectin in conditioned media. The impact of EPCs on platelet aggregation and thrombus formation was investigated in P-selectin deficient (P-sel<sup>-/-</sup>) mice and their wild-type (WT) counterparts. Results: EPCs significantly and dose-dependently impaired collagen-induced whole blood platelet aggregation in WT mice, whereas no effects were observed in P-sel<sup>-/-</sup> mice. Moreover, in a ferric chloride-induced arterial thrombosis model, infusion of EPCs significantly reduced thrombus formation in WT, but not in P-sel<sup>-/-</sup> mice. Furthermore, the relative mass of thrombi generated in EPC-treated P-sel<sup>-/-</sup> mice were significantly larger than those in EPC-treated WT mice, and the number of EPCs recruited within the thrombi and along the arterial wall was reduced in P-sel<sup>-/-</sup> mice as compared to WT mice. Conclusion: This study shows that EPCs impair platelet aggregation and reduce thrombus formation via a cellular mechanism involving binding to platelet P-selectin. These findings add new insights into the role of EPC-platelet interactions in the regulation of thrombotic events during vascular repair.

Original languageEnglish
Article number142
JournalJournal of Translational Medicine
Volume13
Issue number1
DOIs
Publication statusPublished - 7 May 2015

Fingerprint

P-Selectin
Endothelial cells
Platelets
Blood Platelets
Thrombosis
Platelet Aggregation
Agglomeration
Endothelial Progenitor Cells
Blood Vessels
Repair
Blood
Epoprostenol
Conditioned Culture Medium
Cardiovascular System
Fibronectins
Cell Communication
Blood Cells
Collagen

Keywords

  • Aggregation
  • Endothelial progenitor cells
  • P-selectin
  • Platelets
  • Thrombosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner. / Abou-Saleh, Haissam; Hachem, Ahmed; Yacoub, Daniel; Gillis, Marc Antoine; Merhi, Yahye.

In: Journal of Translational Medicine, Vol. 13, No. 1, 142, 07.05.2015.

Research output: Contribution to journalArticle

Abou-Saleh, Haissam ; Hachem, Ahmed ; Yacoub, Daniel ; Gillis, Marc Antoine ; Merhi, Yahye. / Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner. In: Journal of Translational Medicine. 2015 ; Vol. 13, No. 1.
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N2 - Background: The role of endothelial progenitor cells (EPCs) in vascular repair is related to their recruitment at the sites of injury and their interaction with different components of the circulatory system. We have previously shown that EPCs bind and inhibit platelet function and impair thrombus formation via prostacyclin secretion, but the role of EPC binding to platelet P-selectin in this process has not been fully characterized. In the present study, we assessed the impact of EPCs on thrombus formation and we addressed the implication of P-selectin in this process. Methods: EPCs were generated from human peripheral blood mononuclear cells cultured on fibronectin in conditioned media. The impact of EPCs on platelet aggregation and thrombus formation was investigated in P-selectin deficient (P-sel-/-) mice and their wild-type (WT) counterparts. Results: EPCs significantly and dose-dependently impaired collagen-induced whole blood platelet aggregation in WT mice, whereas no effects were observed in P-sel-/- mice. Moreover, in a ferric chloride-induced arterial thrombosis model, infusion of EPCs significantly reduced thrombus formation in WT, but not in P-sel-/- mice. Furthermore, the relative mass of thrombi generated in EPC-treated P-sel-/- mice were significantly larger than those in EPC-treated WT mice, and the number of EPCs recruited within the thrombi and along the arterial wall was reduced in P-sel-/- mice as compared to WT mice. Conclusion: This study shows that EPCs impair platelet aggregation and reduce thrombus formation via a cellular mechanism involving binding to platelet P-selectin. These findings add new insights into the role of EPC-platelet interactions in the regulation of thrombotic events during vascular repair.

AB - Background: The role of endothelial progenitor cells (EPCs) in vascular repair is related to their recruitment at the sites of injury and their interaction with different components of the circulatory system. We have previously shown that EPCs bind and inhibit platelet function and impair thrombus formation via prostacyclin secretion, but the role of EPC binding to platelet P-selectin in this process has not been fully characterized. In the present study, we assessed the impact of EPCs on thrombus formation and we addressed the implication of P-selectin in this process. Methods: EPCs were generated from human peripheral blood mononuclear cells cultured on fibronectin in conditioned media. The impact of EPCs on platelet aggregation and thrombus formation was investigated in P-selectin deficient (P-sel-/-) mice and their wild-type (WT) counterparts. Results: EPCs significantly and dose-dependently impaired collagen-induced whole blood platelet aggregation in WT mice, whereas no effects were observed in P-sel-/- mice. Moreover, in a ferric chloride-induced arterial thrombosis model, infusion of EPCs significantly reduced thrombus formation in WT, but not in P-sel-/- mice. Furthermore, the relative mass of thrombi generated in EPC-treated P-sel-/- mice were significantly larger than those in EPC-treated WT mice, and the number of EPCs recruited within the thrombi and along the arterial wall was reduced in P-sel-/- mice as compared to WT mice. Conclusion: This study shows that EPCs impair platelet aggregation and reduce thrombus formation via a cellular mechanism involving binding to platelet P-selectin. These findings add new insights into the role of EPC-platelet interactions in the regulation of thrombotic events during vascular repair.

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